维生素E对阿霉素肾毒性抑制作用的研究(2)

　　早期研究报道VE既可优化DXR对肿瘤的治疗又不干扰其疗效[5～7]，同时其他研究人员也发现VE可加强DXR的毒性[6]或者对DXR的疗效无任何作用[8，9]。

　　本研究还发现用DXR和VE共同处理细胞后，其毒性作用可被消弱。DXR+0.1 mmol VE组在处理细胞12 h后彗尾长度可减小到(11.01±1.52) μm，但是在2 h及8 h与DXR组相比无明显变化。但是较高浓度1 mmol VE和DXR共同处理细胞时在三个时间段，彗尾长度与DXR相比都明显变短。这说明了VE抑制DXR的作用有一定的时间剂量效应，其原因可能是VE是较强的抗氧化剂，具有清除自由基的作用。

　　综上所述，DXR造成了肾小球内皮细胞的DNA的损伤，而VE能抑制DXR对细胞DNA的损伤作用，因此可对抗DXR的肾毒性。

　　【】

　　[1] Halliwell B, Gutteridge JMC. Comments on review of Free Radicals in Biology and Medicine, second edition, by Barry Halliwell and John M. C. Gutteridge[J]. Free Radic Biol Med，1992，12(1)：9395.

　　[2] Gotoh N, Noguchi N, Tsuchiya J,et al. Inhibition of oxidation of low density lipoprotein by vitamin E and related compounds[J].Free Radic Res，1996 ，24(2)：123134.

　　[3] Dominguez睷odriguez JR, Gomez睠ontreras PC, Hernandez睩lores G,et al.In vivo ihibition by antioxidants of adriamycin-induced apoptosis in murine peritoneal macrophages[J]. Anticancer Res，2001， 21：18691872.

　　[4] Singh NP, Danner DB, Tice RR,et al. Abundant alkali瞫ensitive sites in DNA of human and mouse sperm [J] .Exp Cell Res, 1989,184(2): 461470.

　　[5] Geetha A, Sankar R, Marar T,et al. Alpha tocopherol reduces doxorubicin瞚nduced toxicity in rats瞙istological and biochemical evidences[J]. Ind J Physiol.Pharmacol, 1990,34:94100.

　　[6] Milei J, Boveris A, Llesuy S,et al. Amelioration of adriamycin induced cardiotoxicity in rabbits by prenylamine and vitamins A and E[J]. Am Heart J, 1986,111: 95102.

　　[7] Alberts DS, Peng YM, Moon TE. Alpha瞭ocopherol pretreatment increases adriamycin bone marrow toxicity[J]. Biomedical ,1978, 29:189191.

　　[8] Breed JG, Zimmerman AN, Dormans JA, et al. Failure of the antioxidant vitamin E to protect against adriamycin-induced cardiotoxicity in the rabbit[J]. Cancer Res,1980,40: 20332038.

　　[9] Legha SS, Wang YM, Mackay B,et al. Clinical and pharmacologic investigation of the effects of alpha瞭ocopherol on adriamycin cardiotoxicity[J]. Ann New York Acad Sci, 1982,393:411418.